RBN012759 / Ribon Therap - LARVOL DELTA

PARP14 promotes the growth and glycolysis of acute myeloid leukemia cells by regulating HIF-1α expression. (PubMed, Clin Immunol) - "PARP14 induces AML cell growth and glycolysis by activating NF-κB and promoting HIF-1α expression, which may suggest new insights into the pathogenesis of AML."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • HIF1A

Selective Pharmaceutical Inhibition of PARP14 Mitigates Allergen-Induced IgE and Mucus Overproduction in a Mouse Model of Pulmonary Allergic Response. (PubMed, Immunohorizons) - "Using BALB/c mice sensitized to the allergen Alternaria alternata, we show that peroral administration of RBN012759, a highly selective inhibitor of ADP-ribosylation by PARP14 with negligible impact on other members of the PARP gene family, achieved biologically active plasma concentrations and altered several responses to the Ag. Specifically, the pharmaceutical compound decreased mucus after allergen challenge, blunted the induced increases in circulating IgE, and prevented suppression of IgG2a. We conclude that PARP14 catalytic activity can contribute to pathogenesis in allergic or atopic processes and propose that other biological endpoints dependent on ADP-ribosylation by PARP14 can be targeted using selective inhibition."

Journal • Preclinical • Allergy • Asthma • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • IL13 • IL4 • STAT6

[VIRTUAL] Targeted degradation of PARP14 Using a heterobifunctional small molecule (AACR 2021) - "We have previously shown that the potent and reversible enzymatic inhibitor, RBN012759 (IC50 1,000-fold selective over polyPARPs), links PARP14 catalytic inhibition with suppression of the antitumor immune response in human primary macrophages and human kidney cancer explants...In human primary macrophages PARP14 degradation by RBN012811 led to a dose-dependent decrease of IL-10 release induced by IL-4 stimulation. Our data demonstrates that RBN012811 is a useful tool to enable further exploration of the role of PARP14 in inflammation and cancer."

Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CRBN • IL10 • IL4

A potent and selective PARP14 inhibitor decreases protumor macrophage gene expression and elicits inflammatory responses in tumor explants. (PubMed, Cell Chem Biol) - "Inhibition of PARP14 with RBN012759 reverses IL-4-driven protumor gene expression in macrophages and induces an inflammatory mRNA signature similar to that induced by immune checkpoint inhibitor therapy in primary human tumor explants. These data support an immune suppressive role of PARP14 in tumors and suggest potential utility of PARP14 inhibitors in the treatment of cancer."

IO biomarker • Journal • Immune Modulation • Inflammation • Oncology • IL4